Our long term objective is to devise and provide for clinical evaluation synthetic oligodeoxynucleotides and modifications thereof described in this application. It is expected that these oligomers will enter cells and hybridized with conserved essential segments of HIV genomic RNA, with resultant inhibition of replication and expression of the virus. The main focus of our approach will be on H9 and similar human cells grown in tissue culture, with measurement of inhibitory effects of "antisense" oligomers (and to a lesser extent other oligomers such as "sense" oligomers not included in this term) on syncytia formation, and on viral P17 and P24 antigen expression in infected cells. We will also scale up the production of oligomers in order to make possible toxicity, pharmacodynamic, and pathologic studies on animals, leading toward human trials. Human trials will not however be a direct goal of the present program. We will rely on collaborations to be worked out in the future in consultation with the FDA and NIAID Cooperative program for the pharmacodynamic and pathologic investigations, in which we will supply the necessary amounts of oligomers. We will join in testing the possible therapeutic effect of oligomers on model systems in which HIV grows, when such systems (such as the mouse and rabbit ones) become available for collaborative efforts in which we supply the oligomers.